Drug Market Info presents Cystic Fibrosis Notes & Notable, an interview series with leading voices in the fight to cure Cystic Fibrosis.

Today’s interview is with Dr. Brian O’Sullivan, Cystic Fibrosis Center Director and Professor of Pediatrics at the University of Massachusetts Medical School. Dr. O’Sullivan, who has been working with CF since 1987, was asked to comment on recent developments in the treatment of Cystic Fibrosis. Here are his comments:

What are the biggest hurdles to treating CF?

The single biggest hurdle is patient adherence to medication usage. We ask them to do so much and many of the therapies are very time consuming (nebulizers and chest physical therapy). It is hard for patients to do all that they should.

What are the top advances that you have seen in last five years for CF patients and what is on the horizon?

Kalydeco (recently launched) and the other Vertex compound (VX-809) in clinical development are the top advances. Hopefully other approaches to the basic CF defect will continue to be developed in the next five years for Cystic Fibrosis. I am also looking forward to PTC Therapeutics Ataluran (PTC-124) Phase 3 trial results. Gene therapy studies will be important going forward.

In your opinion, what are the major benefits and drawbacks of Vertex’s recently approved Kalydeco?

The major drawback for Kalydeco is the limited applicability. FDA approval is needed for all Type 3 mutations, not just G551D. The cost ($300,000 a year) is just too much for patients and insurers to swallow. Obviously, if more patients are eligible to use it the cost can come down.

Do most CF patients already know their specific CF mutation and when is this genetic testing usually performed?

Genetic testing has become the norm, especially with newborn screening algorithms that include it. A lot of patients do not know their specific mutations off the top of their heads but they know to ask about them.

Can you tell us a little more about the G551D mutation? Is it hard to detect?

G551D is a mutation which is included on all newborn screening and OB/GYN screening panels, thus it is not hard to detect.

In general, are CF patients with the G551D mutation affected more or less severely than those with other mutations or are they about the same?

G551D is a class 3 mutation. This class is considered to be severe since it leads to loss of function of the CFTR protein.

How will Kalydeco change CF treatment in those patients qualified to use it? Do you believe that Kalydeco could have an impact on CF life span?

I believe Kalydeco will increase CF lifespan. Unfortunately, we still do not have enough data on potential side effects. Until it is used in thousands of patients for several years, we will not know the full consequences (for better and for worse) of its action. If it is as good as we hope, it could lead to decreased need for other therapies, which would offset its cost somewhat. The pivotal study involved subjects continuing their usual medical routine, so we have no idea if the benefits seen with it will be present in the absence of other routine CF care.

The mutation occurs in about approximately 1,200 people in the US or 4% with CF, so can you try to quantify the impact that Kalydeco will have on treating the disease as a whole?

We are nibbling at the edges. Kalydeco will not affect the vast majority of CF patients. However, it does provide hope for others that their mutations may too succumb to small molecule therapy.

About Dr. Brian O’Sullivan

Dr. O’Sullivan is a pediatric pulmonologist and the Cystic Fibrosis Center Director at UMass Memorial Medical Center in Worcester, MA. He has served as Chair of the UMass Medical School IRB for the past 10 years. He co-chaired the pulmonary care guidelines committee for the National Cystic Fibrosis Foundation and has served on their Center Directors Committee.